This study aimed to compare the Hamilton anxiety rating/Hamilton depression rating (HAMA/HAMD) scale scores and blood pressure (BP) goal achievement associated with the use of valsartan–amlodipine single-pill combinations (SPCs) versus valsartan and amlodipine combination in adult hypertensive patients. A total of 476 hypertensive patients were randomly assigned into the SPC (valsartan–amlodipine) and control (valsartan and amlodipine combination) groups. All patients had an uncontrolled BP (160–179/100–109 mm Hg). BP goal was <140/90 mm Hg. Cox proportional hazards regression analysis was used to analyze the likelihood of HAMA/HAMD scales, SPCs, control group, and daily dosage number. Kaplan–Meier analysis was used to estimate the rates of BP goal achievement over time among the 2 groups. A total of 476 patients were included in the study, and 439 patients completed the follow-up and received the index drug therapy. There was a significant difference in BP between the 2 groups on days 28, 42, and 56. Patients who received SPCs had a significantly higher rate of BP goal achievement over time (P = .000). The average HAMD scores in the SPC and control groups were 5.54 and 5.49 and 6.06 and 6.21 on days 28 and 56, respectively. The average HAMA scores in the SPC and control groups were 7.41 and 7.13 and 7.90 and 8.01 on days 28 and 56, respectively. The means of HAMD and HAMA scores were 5.826 and 7.614, respectively. The higher the HAMA/HAMD scores, the lower was the BP goal achievement. The number of drugs taken by the patients was associated with the HAMA and HAMD scores. There was no significant difference between HAMA scores of patients taking 1 tablet daily (7.22 ± 1.885) and those taking two-tablets daily (7.38 ± 1.953) (P = .408). However, when these scores were compared to those of patients taking 4 tablets daily (8.08 ± 2.285), a significant difference was observed (P = .000, P = .000). Hypertensive patients treated with valsartan–amlodipine SPCs were significantly more likely to achieve BP goal and have lesser HAMA/HAMD scores compared to patients treated with valsartan and amlodipine combination.